tbuckley/cabot-search huggingface dataset:
AB0215 DOES THE PARITY IMPROVE THE RHEUMATOID ARTHRITIS ACTIVITY?
Authors: E. Rabhi, H. Ferjani, D. Ben Nessib, L. Kharrat, W. Triki, K. Maatallah, D. Kaffel, W. Hamdi
Journal: Annals of the Rheumatic Diseases (2022)

Background The parity seems to decrease the risk of auto-immune diseases like Rheumatoid arthritis (RA). The risk reduction appeared when the parity number reached two [1]. The activity of RA improved during pregnancy and flares postpartum, but the relationship of parity to RA prognosis is unclear. The impact of childbirth on disease activity is less studied. Objectives We aimed to investigate the impact of parity on rheumatoid arthritis activity. Methods We conducted a retrospective study including patients fulfilling the American Congress Of Rheumatology / European League Against Rheumatism (ACR EULAR) 2010 criteria. We collected epidemiological, clinical, biological (C-reactive protein: CRP, erythrocyte sedimentation rate (ESR), immunological status (rheumatoid factor RF and anti-citrullinated protein/peptide antibody ACPA), and disease activity index (The Disease Activity Score 28 DAS 28). We divided our patients into two groups: group (G1): the nulliparous women; group 2 (G2): women who gave birth. Results Ninety-two patients were enrolled. There were 14 men and 78 women. The mean age was 59.56 ± 11.7 years. The mean disease duration was 9.32 ± 8.22 years. Among 78 women, we found 50 patients with parity. The main swollen joint was 3.34 ± 3.6 in G2 versus 4.44 ± 4.04 in G1 (p=0.94). The mean painful joints were 6.74 ± 5.12 and 9 ± 9.19 (p=0.28), respectively. However, the inflammatory syndrome is higher among women in G2. The mean CRP level was 15.1 mg/l, and the mean ESR was 37.7 mm. In G1, the RF and ACPA were 131 UI/l and 281 UI/l, respectively compared with 568 UI/L and 315UI/l, respectively in G2. A significant difference was noted in the DAS28-CRP between the two groups (G2: 4.18 ±1.23 versus G1: 4.49 ± 2.5, p=0.04). However, no association was found between parity and disease activity using the DAS28-ESR. Conclusion Our study showed that parity could have a protective effect on disease activity. It seems to be associated with a lower joint count and a lower rate of RF and ACPA. However, more studies are necessary to conclude these issues. References [1]Chen WMY, Subesinghe S, Muller S, Hider SL, Mallen CD, Scott IC. The association between gravidity, parity and the risk of developing rheumatoid arthritis: A systematic review and meta-analysis. Semin Arthritis Rheum. avr 2020;50(2):252‑60. Disclosure of Interests None declared
AB0698 IMPACT OF ILOPROST WITHDRAWAL IN SCLERODERMA PATIENTS DUE TO COVID-19 PANDEMIC
Authors: L. Verardi, E. de Lorenzis, G. Natalello, L. Gigante, P. G. Cerasuolo, M. A. D’Agostino, S. L. Bosello
Journal: Annals of the Rheumatic Diseases (2022)

Background Intravenous iloprost is currently recommended in the treatment of Raynaud’s phenomenon (RP) refractory to oral therapy and of digital ulcers (DUs) related to systemic sclerosis (SSc). In real-life practice there is a huge heterogeneity about the Iloprost regimens used, because of a lack of specific recommendations. Coronavirus pandemic resulted in an unexpected emergency leading to sudden and synchronous withdrawal of programmed iloprost infusions for most SSc patients in March 2020, in order to limit virus dissemination. At the same time, lockdown forced people to stay at home, thus reducing the exposure to coldness. Both these unavoidable circumstances were close to an experimental condition, clearly non-replicable in routine conditions. Objectives The aim of the survey was to evaluate the consequences related to a sudden and simultaneous iloprost discontinuation in a cohort of SSc patients. Methods A telephone survey was carried out on SSc patients that interrupted Iloprost infusion at our centre. They were specifically asked to compare acral vascular symptoms just before Iloprost withdrawal, in February and just after the missed infusion in March (0-10 scale). Demographic and disease characteristics, severity and frequency of RP, new DUs onset or aggravation of those pre-existing were reported for each patient. Last available capillaroscopic images were also evaluated to assess the pattern. Results The analysis included 50 patients. After iloprost withdrawal, 11 patients reported a RP worsening because of enhanced intensity (4.6±2.1 vs 5.2±2.3, p=0.007). Only 8 patients of them also complained of an increased frequency (4.5±2.3 vs 5.0±2.4, p=0.07). None of the patients experienced digital ulcers for the first time during quarantine. Among the 27 patients with a history of digital ulcers, 9 reported worsening and 7 recurrences of DUs. Overall, 17 patients (34.0%) complained of a worsening of SSc vascular acral manifestations, namely RP or DUs. Disease and general features did not statistically correlate with worsening of RP except for reduced capillary density. Of note, each unit increase of capillary density corresponds to an average 44% decrease in the odds of RP worsening (OR 0.56, CI 95% 0.36-0.97, p=0.037). History of DUs - either active or former at the time of iloprost discontinuation - was the only clinical predictor of worsening of DU severity. As for RP worsening, the worsening of DU was associated with a lower capillary density. Conclusion Low capillary density can predict a worsening of both RP and DUs within a month after iloprost discontinuation in SSc patients. Further studies are needed to assess whether the capillaroscopy should be used to personalize iloprost regimen in SSc patients. Disclosure of Interests None declared
AB1080 BRUCELLAR SPONDYLODISCITIS: EPIDEMIOLOGICAL, CLINICAL AND BIOLOGICAL ASPECTS
Authors: S. Rekik, S. Boussaid, H. Tbini, S. Jemmali, S. Rahmouni, K. Zouaoui, H. Sahli, M. Elleuch
Journal: Annals of the Rheumatic Diseases (2022)

Background Brucellosis is a systemic infection characterized by significant clinical polymorphism and non-specific manifestations. The spine is a common location for brucellosis. Objectives The aim of this study was to describe the epidemiological, clinical and biological characteristics of brucellar spondylodiscitis. Methods A retrospective study over a period of 15 years, including 18 patients diagnosed with brucellar spondylodiscitis on clinical, biological and/or imaging data. Results Eighteen cases were collected (13 men and 5 woman). The mean age was 52 years [19-76]. The main symptom was unifocal or diffuse spinal pain associated or not with radiculalgia. Inflammatory pain was reported in 12 cases. Thirteen patients consumed raw milk, eleven had contact with farm animals or professional exposure. The average duration of symptoms was 5.7 months [0.5-12], the disease had a progressive onset in 13 patients. The general signs were frequent: deterioration of general condition (13 cases), fever (12 cases) and night sweats (6 cases). All patients had a biological inflammatory syndrome. Wright’s serology, performed in 17 patients, was positive in 15 cases. The Rose Bengal test was positive in 13 of the 15 patients tested. Diagnosis by indirect immunofluorescence, performed in 11 patients, was positive in nine cases. However, the blood cultures, carried out in 13 patients and the disco-vertebral biopsy, carried out in 9 patients, did not find the causal agent. Conclusion The diagnosis of brucellar spondylodiscitis must be based on epidemiological, clinical arguments and biological examinations. Immunological examinations, however, seem to be more contributory and should be performed in case of diagnostic doubt and negative bacteriological investigation. Disclosure of Interests None declared
POS1169 THE INFLAMMATION INDUCED BY MONOSODIUM URATE AND CALCIUM PYROPHOSPHATE CRYSTALS DEPENDS ON OSMOLARITY AND AQUAPORIN CHANNELS.
Authors: T. W. Chirayath, N. Pham, C. Duranton, I. Rubera, A. Gauffenic, M. Cohen Solal, A. Latourte, T. Bardin, P. Richette, F. Lioté, H. K. Ea
Journal: Annals of the Rheumatic Diseases (2022)

Background The inflammation induced by monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals is driven by interleukin (IL)-1β production. This later relies on NLRP3 inflammasome which can be activated by variation of ion concentration. Objectives To assess the role of osmolarity and water flux in MSU and CPP crystal-induced inflammation. Methods In vitro, THP1 monocytes were stimulated by pyrogen-free synthetic MSU and CPP crystals in iso-, hypo- or hyperosmotic media. Cytokine production was quantified by ELISA in cell culture supernatants. Cell size was measured using video microscopy. The role of aquaporin channels was assessed by pharmacological inhibitor (mercury chloride, HgCl2). In vivo, murine air pouch model was used. MSU and CPP crystals were injected in air pouch of mice treated or not with HgCl2 or mannitol. Osmolarity of mouse sera and patient synovial fluids (SF) were measured using freezing point osmometer. The size of cells collected from SF was assessed with imageJ software. Results MSU and CPP crystal-induced IL-1β production was substantially reduced by HgCl2 treatment (MSU 4900 vs 880 pg/ml; CPP 10500 vs 980, p&lt;0.0001) or when cells were cultured in hyperosmotic medium. MSU and CPP crystals induced a transient increase in cell size which was 1.6 and 1.5 bigger after 30 and 100 min of stimulation by MSU and CPP crystals, respectively. After 150 min of stimulation, cell size decreased to their baseline size. Cell size increase was abolished by HgCl2 or hyperosmotic medium. In vivo, MSU and CPP crystal-induced inflammation (assessed by cell infiltration, IL-1β and CXCL2 production in air pouch lavage) was drastically reduced by HgCl2 or mannitol treatment. The serum osmolarity was higher in mannitol-treated mice than untreated mice (320 vs 300 mmosm/L). In patients, cells collected from SF during CPP or MSU crystal-induced flares had a bigger size than cells collected from osteoarthitic SF. The osmolarity of MSU or CPP crystal-containing SF was lower than the osmolarity of osteoarthritic SF (270 vs 310 mmosm/L). Finally, the IL-1β concentration in SF was strongly correlated with cell size and SF osmolarity. Conclusion These results suggest that the variation of osmolarity plays central role in MSU and CPP crystal-induced inflammation. Deciphering how crystals modulate osmolarity will identify new therapeutic targets. Disclosure of Interests None declared
AB0393 SURVIVAL ON JANUS KINASE INHIBITORS VERSUS OTHER ADVANCED THERAPIES IN RHEUMATOID ARTHRITIS
Authors: N. Bakhtiar, L. Gray, S. M. Bilgrami, L. Ottewell, F. Wood, M. Bukhari
Journal: Annals of the Rheumatic Diseases (2022)

Background Four Janus Kinase inhibitors (JAKi) are licensed in the UK for treating rheumatoid arthritis (Upadacitinib, Tofacitinib, Filgotinib and Baricitinib). Several analyses have examined the survival in these groups of drugs and found them more likely to be tolerated more or equivalently than other modes of action. Recent data suggested an age influence on survival on these drugs. Objectives To study the overall survival rates of JAKi compared to the other biologic treatments in a single centre cohort. Methods We analysed patients commencing advanced treatments (anti-Tumour necrosis factor, Interleukin 6 blocker, Rituximab and Abatacept) between February 2011 and October 2021. Variables examined included gender and age. The time on drug was compared between JAKi and other treatments using student’s T test. Chi squared test was used to compare categorical variables. A Cox regression model was fitted to compare length of stay on each agent JAKi length of stay was compared to length of stay on other agents combined. Results 592 patients were included in the analysis. 168 (28%) were started on JAKi. 435 (73.48%) were females. Mean age at drug start was 60.6 years (SD 13.5). The numbers on drug were Filgotinib n=10, Tofacitinib n=35, Upadacitinib n=37, Baricitinib n=86, Adalimumab n=211, Abatacept n=36, Certolizumab n=18, Etanercept n=112, Golimumab n=21 and Tocilizumab n=26. 93 (15.7%) discontinued their drug, mostly due to lack of efficacy. Mean number of days on any biologic treatment was 918.9 (SD 711.5). Patients on JAKi had a significantly shorter survival on drug 652.7 days vs 1024.4 days (P&lt;0.001). There were no significant differences in age and gender between the groups. Univariate regression showed a hazard ratio of 1.19 (95%CI 0.75,1.98). This remained non-significant after adjusting for age and gender (1.18 95%CI 0.71,1.95). The only predictor of stoppage was age (HR 1.03 95%CI 1.01,1.04). Conclusion In this relatively large observational study, there was no difference in predictors of stoppage between JAKi and other advanced therapies. Increasing age was found to be a predictor for stoppage. This is in line with other reports in the literature. Further work looking at the impact of serology and disease activity will be performed. Disclosure of Interests Nauman Bakhtiar: None declared, Leanne Gray: None declared, Syed Mujtaba Bilgrami Grant/research support from: Grants for BSR &amp; EULAR Conferences in the past., Lesley Ottewell: None declared, Fiona Wood: None declared, Marwan Bukhari Speakers bureau: Bristol-Myers Squib, UCB celltech, Roche/Chugai, Pfizer, Abbvie, Merck, Mennarini, Sanofi-aventis, Eli-Lilly, Janssen, Amgen, Novartis and Gilead
POS0780 MONOGENIC SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IN NORTHERN ISRAEL
Authors: I. Spivak, T. Hershkovitz, R. Zaid, K. Weiss, Y. Butbul Aviel
Journal: Annals of the Rheumatic Diseases (2022)

Background Systemic Lupus erythematous (SLE) is a heterogenic clinical syndrome with a multifactorial etiology including diverse environmental, immunological and genetic causes and modifiers. Increasingly, utilizing next generation sequencing tooIs, monogenic forms of SLE have been identified. Objectives The aim of our study was to identify monogenic causes of SLE in the unique pediatric population of Northern Israel. Methods A retrospective and prospective study was carried out between 2010-2021 in a single tertiary pediatric medical center. Genetic testing including Whole exome sequencing (WES) was performed for select patients including family history of SLE, consanguinity and\or clinical findings suggestive of specific disorder. Results 75 children were diagnosed with SLE. 13/75 had one or more relatives with SLE, including a pedigree with 4 affected members. Mean age at presentation was 10.1±4.7. A monogenic disorder was identified in total of 7/75 of pedigrees. Four patients were diagnosed with Prolidase deficiency, one patient with ADAR1 mutation related to Aicardi–Goutières syndrome and one pedegree with APC5 mutations. Candidate variants in genes related to immune system were identified in one proband and her father requiring further study. Additional WES results are pending Conclusion We detected monogenic causes of SLE in a select cohort of patient in Northern Israel. Identification of a genetic basis for disease has direct clinical implication for patients and families and can also enhance our understanding of the pathogenesis and disease mechanisms involved in the more common sporadic forms of SLE. Disclosure of Interests ilia spivak: None declared, Tova Hershkovitz1 Grant/research support from: Regeneron Genetics center, Tarrytown, NY, USA, Rinat Zaid Grant/research support from: Regeneron Genetics center, Tarrytown, NY, USA, Karin Weiss Grant/research support from: Regeneron Genetics center, Tarrytown, NY, USA, Yonatan Butbul Aviel: None declared
AB0136 ELUCIDATING THE PATHOGENIC EFFECTS OF ANTI-TOPOISOMERASE-1 ANTIBODIES IN SYSTEMIC SCLEROSIS
Authors: M. Aspari, K. V. Petersen, J. Geertsen Keller, S. R. Greisen, K. Soendergaard, J. Hauge Mikkelsen, B. Knudsen, B. Deleuran
Journal: Annals of the Rheumatic Diseases (2022)

Background Prediction of the pattern of organ involvement in patients with diffuse cutaneous systemic sclerosis (dcSSc) is supported by the specificity of autoantibodies. These autoantibodies are generally mutually exclusive and highly specific for dcSSc 1 . The autoantibody reactivity allows patients to be stratified early in the disease course, leading to a tailored approach and management. Anti-topoisomerase I antibodies (ATA) are predictors of the development of interstitial lung disease (ILD) and digital ulcers but appear to be protective against pulmonary artery hypertension (PAH). Objectives The aim of this project was to elucidate the functioning of ATA and their role in the pathogenicity of the disease. Methods Sera from healthy volunteers (HV) and dcSSc patients with and without ATA were collected from Aarhus University Hospital. Total IgG was purified from the sera using a Protein G column. ATA was further purified from the total IgG fraction by passing it through a column packed with the functional domains of human topoisomerase-1 (TOP1) expressed from E.coli. Sera, total IgG and purified ATA fractions were utilized in preliminary experiments. The ability of ATA to inhibit TOP1 was tested by a in house developed REEAD assay in which the generation of closed DNA circles, by the cleavage-ligation activity of TOP1, is monitored after rolling circle amplification 2 . Results Serum from patients with dcSSc, but not from HV, could inhibit TOP1 activity at various dilutions. Similarly, purified total IgG fractions from dcSSc patients could also inhibit TOP1 activity. ATA was successfully separated from IgG from dcSSc patients who were positive for ATA. This could inhibit TOP1 activity even at lower concentrations than total IgG. This was the case for both mitochondrial and nuclear TOP1 activity. Fully in line with presence of ATA, PBMC’s from dcSSc patients contained a lower TOP1 activity compared to HVs PBMCs. Conclusion To our knowledge we are the first group to be able to successfully separate ATA from total IgG from dcSSc patients. our unique in house developed REEAD assay clearly demonstrates the function of ATA and provides the opportunity to better understand References [1]Role of autoantibodies in the diagnosis and prognosis of interstitial lung disease in autoimmune rheumatic disorders. Masataka Kuwana, Albert Gil-Vila and Albert Selva-O’Callaghan, Ther Adv Musculoskel Dis 2021, Vol. 13: 1–17 DOI: 10.1177/ [2]Rolling circle amplification based detection of human topoisomerase I activity on magnetic beads. Zuccaro, Laura; Tesauro, Cinzia; Cerroni, Barbara; Ottaviani, Alessio; Knudsen, Birgitta Ruth; Balasubramanian, Kannan; Desideri, Alessandro. Analytical Biochemistry, Bind 451, 15.04.2014, s. 42-44. Disclosure of Interests None declared
The Climate Emergency and the Health of Our Patients: The Role of the Rheumatologist
Authors: Paul F. Dellaripa, Thomas Bush, Frederick W. Miller, Candace H. Feldman
Journal: Arthritis & Rheumatology (2022)

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The Underuse of Medicare's Prevention and Coordination Codes in Primary Care
Authors: Sumit D. Agarwal, Sanjay Basu, Bruce E. Landon
Journal: Annals of Internal Medicine (2022)

Background: Efforts to better support primary care include the addition of primary care–focused billing codes to the Medicare Physician Fee Schedule (MPFS). Objective: To examine potential and actual use by primary care physicians (PCPs) of the prevention and coordination codes that have been added to the MPFS. Design: Cross-sectional and modeling study. Setting: Nationally representative claims and survey data. Participants: Medicare patients. Measurements: Frequency of use and estimated Medicare revenue involving 34 billing codes representing prevention and coordination services for which PCPs could but do not necessarily bill. Results: Eligibility among Medicare patients for each service ranged from 8.8% to 100%. Among eligible patients, the median use of billing codes was 2.3%, even though PCPs provided code-appropriate services to more patients, for example, to 5.0% to 60.6% of patients eligible for prevention services. If a PCP provided and billed all prevention and coordination services to half of all eligible patients, the PCP could add to the practice's annual revenue $124 435 (interquartile range [IQR], $30 654 to $226 813) for prevention services and $86 082 (IQR, $18 011 to $154 152) for coordination services. Limitation: Service provision based on survey questions may not reflect all billing requirements; revenues do not incorporate the compliance, billing, and opportunity costs that may be incurred when using these codes. Conclusion: Primary care physicians forego considerable amounts of revenue because they infrequently use billing codes for prevention and coordination services despite having eligible patients and providing code-appropriate services to some of those patients. Therefore, creating additional billing codes for distinct activities in the MPFS may not be an effective strategy for supporting primary care. Primary Funding Source: National Institute on Aging.
AB0235 TREAT TO TARGET PATHWAY (T2T) IN INFLAMMATORY ARTHRITIS-DESIRABLE RESULTS? AND IF CERTAIN GROUPS RESPOND TO TREATMENT BETTER?
Authors: Q. Shah, E. Ison, B. Whelan, M. O’sullivan, C. Silke
Journal: Annals of the Rheumatic Diseases (2022)

Background There is established evidence that treat to target strategy in inflammatory arthritis helps achieve early remission rates or low disease activity. This approach is more effective for improved outcomes at no additional costs and more likely to achieve rapid and sustained disease control. It is important to aim for early diagnosis to limit the structural damage that occurs with prolonged inflammation. Commencing disease modifying anti-rheumatic drugs (DMARD) therapy and glucocorticoids as early as possible and titrating therapy as appropriate improves clinical outcomes. Objectives Aim of this study was to analyse ACR20 response within different subgroups of inflammatory Arthritis patients enrolled in Treat to Target program. Methods Data collection was performed by assessing electronic medical records of 374 inflammatory arthritis patients who participated in Treat to Target pathway for inflammatory arthritis between 2014 to 2020. In total 374 patients were enrolled in treat to target inflammatory pathway led by Rheumatology ANP with consultant supervision. Majority of the patients had diagnosis of Rheumatoid arthritis as per ACR/Eular criteria. 213(51%) were seropositive RF+, 83(19.9%) were seronegative RF-, 44(10.5%) were diagnosed as psoriatic arthritis, and 34(8.1%) were labelled as undifferentiated inflammatory arthritis. In terms of age and gender, 158(42%) were under 50, and 216(58%) were aged 50 and over, majority females 207(55%). Smoking status 118(32%) current, 211(56%) never, 45(12%) ex-smokers. DMARD started at baseline was Methotrexate only and Starting dose was 15mg for all patients. 326(88%) were on oral methotrexate and only 48(12%) were on SC form between weeks 1-20. ACR 20,50,70 responses were analysed for these subgroups with majority (61%) seen at week 6 for their visit 1 after starting T2T pathway while all patients seen by week 20. Results ACR 20,50 and 70 responses were calculated for all subgroups enrolled in T2T program. The results showed that ACR 20 response rate was same among patients aged under and over 50(67% responders), ACR 50 (38.3%) responders and ACR 70 (20.1%) responders. There was no significant difference in ACR 20 response among females and males (66.9% response) both groups. In terms of seropositivity, 75% responded to treatment in RF+ group vs 60% in RF-group. Higher response rates were seen among not current smokers vs active smokers(70%vs65%). ACR 20 response was greater in patients on Sc form of methotrexate. Overall, 65 % achieved remission within 15 months of starting T2T pathway while remaining achieved low disease activity. Further analysis and discussion will follow. Conclusion Treat to target strategy in inflammatory arthritis are consistent with real world data in achieving early response rates with methotrexate (ACR responses) and specific subgroups within T2T cohort respond better to treatment. Disclosure of Interests None declared